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We integrated multimodal single-cell and spatial profiling from liver cancer mouse models and human metastases to track the spatiotemporal dynamics of DTCs and their microenvironments from single-cell seeding to overt lung metastasis. We identified a residual population of quiescent\n                    <jats:italic toggle=\"yes\">Phgdh<\/jats:italic>\n                    <jats:sup>high<\/jats:sup>\n                    DTCs that survived initial innate immune clearance and became transiently enriched in micrometastases. These cells shaped an immune-scarce microenvironment through PHGDH-dependent, H3K27me3-mediated epigenetic silencing of chemokine transcription, thereby promoting metastatic expansion.\n                    <jats:italic toggle=\"yes\">Cx3cr1<\/jats:italic>\n                    <jats:sup>high<\/jats:sup>\n                    interstitial macrophages were also transiently enriched before DTC expansion, creating an immune-privileged niche for metastatic outgrowth by recruiting immunosuppressive cells. Inactivating the PHGDH-H3K27me3 axis in DTCs or depleting interstitial macrophages restored immune surveillance and inhibited metastatic colonization. These findings provide insights into the development of micrometastasis-targeting regimens.\n                  <\/jats:p>","DOI":"10.1126\/science.adz7928","type":"journal-article","created":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T18:01:01Z","timestamp":1785434461000},"update-policy":"https:\/\/doi.org\/10.34133\/aaas_crossmark","source":"Crossref","is-referenced-by-count":1,"title":["Spatiotemporal multiomics uncover tumor ecosystem dynamics during metastatic colonization"],"prefix":"10.1126","volume":"393","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9790-2761","authenticated-orcid":true,"given":"Yunfan","family":"Sun","sequence":"first","affiliation":[{"name":"Zhongshan-BGI Precision Medical Center, Zhongshan Hospital, Fudan University, Shanghai, China."},{"name":"Department of Hepatobiliary Surgery and Liver Transplantation, Liver Cancer Institute, Zhongshan Hospital, Fudan University, Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Shanghai, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6902-2732","authenticated-orcid":true,"given":"Yu","family":"Zhong","sequence":"additional","affiliation":[{"name":"BGI Research, Chongqing, China."},{"name":"State Key Laboratory of Genome and Multi-omics Technologies, BGI Research, Shenzhen, China."},{"name":"Department of Pathology, College of Basic Medicine, Chongqing Medical University, Chongqing, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shang","family":"Liu","sequence":"additional","affiliation":[{"name":"BGI Research, Chongqing, China."},{"name":"State Key Laboratory of Genome and Multi-omics Technologies, BGI Research, Shenzhen, China."},{"name":"Ruijin Yangtze River Delta Health Institute, Wuxi Branch of Ruijin Hospital, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-6564-8209","authenticated-orcid":true,"given":"Zefan","family":"Zhang","sequence":"additional","affiliation":[{"name":"Zhongshan-BGI Precision Medical Center, Zhongshan Hospital, Fudan University, Shanghai, China."},{"name":"Department of Hepatobiliary Surgery and Liver Transplantation, Liver Cancer Institute, Zhongshan Hospital, Fudan University, Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Shanghai, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-2330-7091","authenticated-orcid":true,"given":"Chunqing","family":"Wang","sequence":"additional","affiliation":[{"name":"BGI Research, Chongqing, China."},{"name":"State Key Laboratory of Genome and Multi-omics Technologies, BGI Research, Shenzhen, China."},{"name":"Department of Pathology, College of Basic Medicine, Chongqing Medical University, 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